The purpose of this project is to investigate surgical problems as they relate to the pulmonary circulation using physiologic, pharmacologic, biochemical and anatomic approaches. The aims of the project are to improve our current understanding of the fundamental mechanisms involved in the regulation of the pulmonary vascular bed in normal and patho-physiologic states using intact animal preparation, isolated tissue studies and biochemical studies. The project is divided into four areas. The first part is concerned with the nature and distribution of autonomic receptors in the pulmonary vascular bed. The second part of the proposal is concerned with the nature of pulmonary vascular responses to vasodilator drugs. The objective of these studies is to determine the mechanism of action of vasodilator drugs and to find new modes of therapy for treatment of cor pulmonale and pulmonary hypertension. The third section of this proposal is concerned with the nature of the response of the pulmonary vascular bed to precapillary hypoxemia and the fourth section is directed toward the effects of lung injury on pulmonary metabolism of vasoactive substances. In these studies right heart and transseptal catheterization techniques will be used to maintain pulmonary blood flow constant in the intact chest animal and measurement of pressure gradients will be used to investigate the site of action of autonomic agonists, sympathetic and parasympathetic nerve stimulation, hypoxia and vasodilator drugs in the pulmonary vascular bed. Results obtained with measurement of pressure gradients will be compared to results obtained using the viscous bolus and venous outflow occlusion technique. The results of these studies may lead to new forms of therapy for treatment of cor pulmonale, pulmonary hypertension and shock lung syndrome.